Oleg Igoshin
Department of Bioengineering
Rice University

Monday, February 11, 2008
4:00PM in 127 Hayes-Healy
*Tea at 3:30 in 257 Hurley*

Uncovering Design Principles of Biochemical Networks

A key property of living cells is their ability to react to internal or external signals with specific biochemical responses. The nature of these responses can only be understood by studying the dynamics of the underlying biochemical networks involving reactions and interactions of genes, proteins and other biochemical components of the cell. Many naturally occurring networks display graded responses in which continuous variation of an input signal results in continuous change of the system output. Alternatively, biochemical networks can exhibit bistable or hysteretic responses so that over a range of signals the network possesses two stable steady states.  Several examples of hysteretic developmental switches have been identified in naturally occurring systems or those constructed synthetically. The generic theme underlying the existence of hysteretic responses in all these circuits is the same – the existence of a positive feedback and signal amplification by an underlying non-linearity. Such bistable designs would be desirable to networks controlling irreversible cell-fate decisions but can be deleterious for networks for environment sensing. Recently we constructed several mathematical models illustrating how the feedback architecture of the networks coupled to post-translational regulation leads to the physiologically desired response. These models include (A) partner-switching mechanisms controlling factors sF and sB in Bacillus subtilis and related bacteria; (B) the network controlling proteases expression in populations of B. subtilis under nutrient limiting conditions and (C) the network controlling differentiation of hematopoietic stem cells. The results of our models will be discussed in terms of evolutionary design principles – how physiological demands shape dynamical responses of biochemical circuits.